Liver-specific catalase expression in transgenic mice inhibits NF-kappaB activation and DNA synthesis induced by the peroxisome proliferator ciprofibrate.
Liver-specific catalase expression in transgenic mice inhibits NF-kappaB activation and DNA synthesis induced by the peroxisome proliferator ciprofibrate.
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转基因小鼠肝脏特异性过氧化氢酶表达抑制过氧化物酶体增殖剂环丙贝特诱导的 NF-κB 激活和 DNA 合成。
DOI：
10.1093/carcin/19.4.631
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发表时间：
1998
期刊：
影响因子：
4.7
通讯作者：
Glauert,HP
中科院分区：
文献类型：
--
作者：
Nilakantan,V;Spear,BT;Glauert,HP
过氧化物酶体增殖物是一组非遗传毒性的肝脏致癌物，已被提出通过增加肝脏中的氧化损伤来起作用。为了验证这一假设，我们研究了过氧化物酶体增殖物处理的小鼠肝脏过氧化氢酶过表达是否影响细胞增殖的诱导或参与细胞增殖的转录因子的激活。转基因小鼠或非转基因同窝仔喂食0.01%环丙贝特或对照饮食21天。过氧化氢酶过表达对脂肪酰辅酶A氧化酶活性没有显著影响，尽管转基因动物中脂肪酰辅酶A氧化酶与过氧化氢酶的比率显著降低。在非转基因小鼠中，环丙贝特显著增加肝细胞中的标记指数，但过氧化氢酶过表达显著抑制这种增加。环丙贝特增加了非转基因小鼠核因子（NF）-κ B的激活，但这种增加被过氧化氢酶过表达抑制。环丙贝特也增加AP-1的激活，但过氧化氢酶过表达并没有显着抑制这种增加，虽然AP-1激活在转基因小鼠低40%。这些结果支持了活性氧在过氧化物酶体增殖剂环丙贝特诱导细胞增殖中发挥作用的假设，因此可能在这些物质的致癌性中发挥重要作用。
Peroxisome proliferators are a group of non-genotoxic hepatic carcinogens that have been proposed to act by increasing oxidative damage in the liver. To test this hypothesis, we have examined if hepatic catalase overexpression in peroxisome proliferator-treated mice influences the induction of cell proliferation or the activation of transcription factors involved in cell proliferation. Transgenic mice or non-transgenic littermates were fed either 0.01% ciprofibrate or a control diet for 21 days. Fatty acyl CoA oxidase activity was not significantly affected by catalase overexpression, although the ratio of fatty acyl CoA oxidase to catalase was significantly decreased in transgenic animals. The labeling index in hepatocytes was significantly increased by ciprofibrate in non-transgenic mice, but catalase overexpression significantly inhibited this increase. Ciprofibrate increased the activation of nuclear factor (NF)-kappaB in non-transgenic mice, but this increase was inhibited by catalase overexpression. Ciprofibrate also increased AP-1 activation, but catalase overexpression did not significantly inhibit this increase, although AP-1 activation was 40% lower in transgenic mice. These results support the hypothesis that active oxygen plays a role in the induction of cell proliferation by the peroxisome proliferator ciprofibrate and therefore may be important in the carcinogenicity of these agents.
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DOI：
--
发表时间：
1995-04
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
M. Fitzgerald;E. Webber;Justine R. Donovan;N. Fausto
通讯作者：
M. Fitzgerald;E. Webber;Justine R. Donovan;N. Fausto
环丙贝特诱导肝癌过程中肝细胞增殖的评价。
影响因子：
9.7
作者：
Yeldandi,AV;Milano,M;Subbarao,V;Reddy,JK;Rao,MS
通讯作者：
Rao,MS
过氧化物酶体增殖和肝癌发生。
影响因子：
4.7
作者：
Rao,MS;Reddy,JK
通讯作者：
Reddy,JK
活性氧中间体作为 NF-xB 转录因子和 HIV-1 激活中明显广泛使用的信使
DOI：
--
发表时间：
1991
期刊：
影响因子：
--
作者：
Laboratorium farMolekulare
通讯作者：
Laboratorium farMolekulare
肝脏生物学和疾病中的主动细胞死亡（细胞凋亡）。
DOI：
--
发表时间：
1995
期刊：
Progress in liver diseases
影响因子：
--
作者：
R. Schulte‐Hermann;W. Bursch;B. Grasl
通讯作者：
B. Grasl